目的:研究骨碎补总黄酮对亚硝酸钠诱导的学习记忆障碍模型小鼠学习记忆的影响。方法:将75只小鼠按随机数字表法分为空白组、模型组、抗脑衰胶囊组、骨碎补总黄酮组和骨碎补总黄酮+抑制剂组，每组15只。抗脑衰胶囊组灌胃抗脑衰胶囊混悬液585 mg/kg；骨碎补总黄酮组灌胃骨碎补总黄酮溶液97.5 mg/kg；骨碎补总黄酮+抑制剂组腹腔注射0.072 mg/kg ICI182780溶液，并灌胃骨碎补总黄酮溶液97.5 mg/kg，连续给药21 d，1次/d。第22天进行造模，除空白组外，其余各组小鼠腹腔注射亚硝酸钠复制学习记忆障碍模型。采用水迷宫试验检测小鼠学习记忆能力，免疫组织化学染色检测小鼠海马雌激素受体β（ERβ）表达，Western blot法检测海马中ERβ、磷酸化p38（P-P38）、Bcl-2、Bcl-2关联死亡启动子（Bcl2 antagonist of cell death，Bad）、Caspase-3蛋白表达，比色法检测海马MDA、SOD、NO水平。结果:与模型组比较，骨碎补总黄酮组小鼠潜伏期缩短（n P<0.01），穿越平台次数及靶象限停留时间增加（n P<0.01）；小鼠海马区ERβ［（0.371±0.010）比（0.124±0.009）］、Bcl-2［（1.146±0.028）比（0.726±0.016）］蛋白表达及SOD［（153.657±6.385）U/mg比（67.719±5.845）U/mg］活性增加（n P<0.01）；P-P38/P38［（0.412±0.043）比（0.806±0.069）］、Bad［（0.421±0.010）比（0.633±0.010）］、Caspase-3［（0.923±0.042）比（1.437±0.033）］蛋白表达及MDA［（8.669±0.662）nmol/mg比（11.772±1.054）nmol/mg］、NO［（4.259±0.225）nmol/mg比（10.805±0.415）nmol/mg］水平降低（n P<0.01）。ER阻断剂可拮抗骨碎补总黄酮的恢复和改善作用。n 结论:骨碎补总黄酮可通过雌激素受体-P38丝裂原激活的蛋白激酶（ER-P38/MAPK）信号通路调节亚硝酸钠模型小鼠的学习记忆功能，抑制神经细胞凋亡，减少氧化应激损伤，从而发挥神经保护作用。“,”Objective:To study the effect of total flavonoids of n Rhizoma Drynariae on learning and memory impairment mice induced by sodium nitrite.n Methods:75 mice were divided into blank group, model group, Kangnaoshuai capsule group, n Rhizoma Drynariae total flavonoids group and n Rhizoma Drynariae total flavonoids+inhibitor group according to the random number table method, with 15 mice in each group. The Kangnaoshui Capsule group was administered with Kangnaoshui Capsule 585 mg/kg, the n Rhizoma Drynariae total flavonoids group was administered with the n Rhizoma Drynariae total flavonoids 97.5 mg/kg, the n Rhizoma Drynariae total flavonoids group and the inhibitor group were administered with the n Rhizoma Drynariae total flavonoids by intragastric administration 97.5 mg/kg, and intraperitoneal injection of 0.072 mg/kg ICI182780 for 21 days, once a day. The model was established on the 22nd day. Except for the blank group, the other mice were injected with sodium nitrite intraperitoneally to replicate the mice model with impaired learning and memory capability. The learning and memory capabilit of mice were detected with water maze method, and the estrogen receptor in hippocampus was detected by immunohistochemistry β (estrogen receptor β, ERβ). The expression of ERβ in hippocampus and the expression of phosphorylated P38 (P-P38) and the protein contents of B-cell lymphoma-2 (Bcl-2), Bcl-2 associated death promoter (Bad) and Caspase-3 in the apoptotic system was detected by Western blot. The kit was used to detect MDA,SOD and NO protein content in hippocampus.n Results:The latency of n Rhizoma Drynariae total flavonoids group was significantly shorter than the model group, the number of crossing platform and the residence time in the target quadrant were significantly increased (n P<0.01); The expression of ERβ Protein in mice hippocampus (0.371 ± 0.010n vs. 0.124 ± 0.009), Bcl-2 protein (1.146 ± 0.028n vs. 0.726 ± 0.016) and the contents of SOD [(153.657 ± 6.385) U/mgn vs. (67.719±5.845) U/mg] increased significantly (n P<0.01); The expression of P-P38/P38 protein (0.412 ± 0.043n vs.0.806 ± 0.069), Bad protein (0.421 ± 0.010n vs.0.633 ± 0.010), Caspase-3 protein (0.923 ± 0.042n vs.1.437 ± 0.033), and the content of MDA [(8.669 ± 0.662) nmol/mgn vs. (11.772 ± 1.054) nmol/mg] and NO [(4.259 ± 0.225) nmol/mgn vs. (10.805 ± 0.415) nmol/mg] decreased significantly (n P<0.01). In addition, ER blocker can antagonize the above recovery and improvement effects ofn Rhizoma Drynariae total flavonoids group.n Conclusion:Rhizoma Drynariae total flavonoids can regulate memory impairment, inhibit neuronal apoptosis and reduce oxidative stress in sodium nitrite model mice through ER-P38/MAPK signal pathway.n